Corporate Banner
Satellite Banner
Genotyping & Gene Expression
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Absence of Gene Leads to Earlier, More Severe Case of Multiple Sclerosis

Published: Tuesday, June 25, 2013
Last Updated: Tuesday, June 25, 2013
Bookmark and Share
UCSF finding in animal study may lead to biomarker that predicts course of disease in humans.

A UC San Francisco-led research team has identified the likely genetic mechanism that causes some patients with multiple sclerosis (MS) to progress more quickly than others to a debilitating stage of the disease. This finding could lead to the development of a test to help physicians tailor treatments for MS patients.

Researchers found that the absence of the gene Tob1 in CD4+ T cells, a type of immune cell, was the key to early onset of more serious disease in an animal model of MS.

Senior author Sergio Baranzini, PhD, a UCSF associate professor of neurology, said the potential development of a test for the gene could predict the course of MS in individual patients.

The study, done in collaboration with UCSF neurology researchers Scott Zamvil, MD, and Jorge Oksenberg, PhD, was published on June 24 in the Journal of Experimental Medicine.

MS is an inflammatory disease in which the protective myelin sheathing that coats nerve fibers in the brain and spinal cord is damaged and ultimately stripped away – a process known as demyelination. During the highly variable course of the disease, a wide range of cognitive, debilitating and painful neurological symptoms can result.

In previously published work, Baranzini and his research team found that patients at an early stage of MS, known as clinically isolated syndrome, who expressed low amounts of Tob1 were more likely to exhibit further signs of disease activity – a condition known as relapsing-remitting multiple sclerosis – earlier than those who expressed normal levels of the gene.

The current study, according to Baranzini, had two goals: to recapitulate in an animal model what the researchers had observed in humans, and uncover the potential mechanism by which it occurs.

The authors were successful on both counts. They found that when an MS-like disease was induced in mice genetically engineered to be deficient in Tob1, the mice had significantly earlier onset compared with wild-type mice, and developed a more aggressive form of the disease.

Subsequent experiments revealed the probable cause: the absence of Tob1 in just CD4+ T cells. The scientists demonstrated this by transferring T cells lacking the Tob1 gene into mice that had no immune systems but had normal Tob1 in all other cells. They found that the mice developed earlier and more severe disease than mice that had normal Tob1 expression in all cells including CD4+.

“This shows that Tob1 only needs to be absent in this one type of immune cell in order to reproduce our initial observations in mice lacking Tob1 in all of their cells,” said Baranzini.
Personalized Treatments for MS Patients

The researchers also found the likely mechanism of disease progression in the Tob1-deficient mice: higher levels of Th1 and Th17 cells, which cause an inflammatory response against myelin, and lower levels of Treg cells, which normally regulate inflammatory responses. The inflammation results in demyelination.

The research is significant for humans, said Baranzini, because the presence or absence of Tob1 in CD4+ cells could eventually serve as a prognostic biomarker that could help clinicians predict the course and severity of MS in individual patients. “This would be useful and important,” he said, “because physicians could decide to switch or modify therapies if they know whether the patient is likely to have an aggressive course of disease, or a more benign course.”

Ultimately, predicted Baranzini, “This may become an example of personalized medicine. When the patient comes to the clinic, we will be able to tailor the therapy based on what the tests tell us. We’re now laying the groundwork for this to happen.”


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,900+ scientific posters on ePosters
  • More than 4,200+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Cat Stem Cell Therapy Gives Humans Hope
By the time Bob the cat came to the UC Davis veterinary hospital, he had used up most of his nine lives.
Monday, February 08, 2016
CRISPR-Cas9 Helps Uncover Genetics of Exotic Organisms
A new study illustrates the ease with which CRISPR-Cas9 can knock out genes in exotic animals to learn how those genes control growth and development.
Friday, December 11, 2015
‘Purity’ Of Tumor Samples May Significantly Bias Genomic Analyses
Non-cancerous tumor components influence research findings, clinical classifications, study shows.
Monday, December 07, 2015
Rare Childhood Leukemia Reveals Surprising Genetic Secrets
A coalition of leukemia researchers led by scientists from UC San Francisco has discovered surprising genetic diversity in juvenile myelomonocytic leukemia (JMML), a rare but aggressive childhood blood cancer.
Thursday, October 15, 2015
Engineers Crack DNA Code of Autoimmune Disorders
Researchers have identified an unexpectedly general set of rules that determine which molecules can cause the immune system to become vulnerable to the autoimmune disorders lupus and psoriasis.
Wednesday, June 10, 2015
May the Cellular Force be With You
Like tiny construction workers, cells sculpt embryonic tissues and organs in 3D space.
Friday, December 13, 2013
Chemical Signature for Fast Form of Parkinson's Found
The physical decline experienced by Parkinson's disease patients eventually leads to disability and a lower quality of life.
Monday, November 25, 2013
Researchers Un-Junking Junk DNA
A study shines a new light on molecular tools our cells use to govern regulated gene expression.
Wednesday, November 13, 2013
Did Inefficient Cellular Machinery Evolve to Fight Viruses and Jumping Genes?
UCSF scientist poses new theory on origins of eukaryotic gene expression.
Monday, November 11, 2013
Single Gene Mutation Linked to Neurological Disorders
Mutation could offer insights into Alzheimer’s, Parkinson’s and Huntigton’s Diseases.
Wednesday, October 16, 2013
Discovery Could Lead to Saliva Test for Pancreatic Cancer
The disease is typically diagnosed through an invasive and complicated biopsy.
Tuesday, October 15, 2013
Dentistry School Receives $5M to Study Saliva Biomarkers
Imagine having a sample of your saliva taken at the dentist's office, and then learning within minutes whether your risk for stomach cancer is higher than normal.
Thursday, August 15, 2013
Brain Anomolies are Potential Biomarkers for Autism
Brain anomalies may serve as potential biomarkers for the early identification of the neurodevelopmental disorder.
Wednesday, July 10, 2013
Second Amyloid May Play a Role in Alzheimer's
The study is the first to identify deposits of the protein, called amylin, in the brains of people with Alzheimer's disease.
Monday, July 01, 2013
Studies Illuminate Functions of RNA
Researchers at the University of California illuminate the functional importance of a relatively new class of RNA molecules.
Tuesday, June 11, 2013
Scientific News
Light Signals from Living Cells
Fluorescent protein markers delivered under high pressure.
Genomic Signature Shared by Five Types of Cancer
National Institutes of Health researchers have identified a striking signature in tumor DNA that occurs in five different types of cancer.
Genetic Mechanism Behind Cancer-Causing Mutations
Researchers at Indiana University has identified a genetic mechanism that is likely to drive mutations that can lead to cancer.
How to Unlock Inaccessible Genes
An international team of biologists has discovered how specialized enzymes remodel the extremely condensed genetic material in the nucleus of cells in order to control which genes can be used.
Viral Gene Editing System Corrects Genetic Liver Disease
Penn study has implications for developing safe therapies for an array of rare diseases via new gene cut-and-paste methods.
Mapping Regulatory Elements
Systematically searching DNA for regulatory elements indicates limits of previous thinking
New Biomarker to Assess Stem Cells Developed
A research team led by scientists from UCL have found a way to assess the viability of 'manufactured' stem cells known as induced pluripotent stem cells (iPSCs). The team's discovery offers a new way to fast-track screening methods used in stem cell research.
'Junk' DNA Plays Role in Preventing Breast Cancer
Supposed "junk" DNA, found in between genes, plays a role in suppressing cancer, according to new research by Universities of Bath and Cambridge.
Genome-Wide Study Yields Markers of Lithium Response
An international consortium of scientists has identified a stretch of chromosome that is associated with responsiveness to the mood-stabilizing medication lithium among patients with bipolar disorder.
A Cancer’s Surprise Origins, Caught in Action
First demonstration of a melanoma arising from a single cell.
SELECTBIO

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,200+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!